Iron Flashcards

1
Q

Why is iron highly toxic?

A

the body has no way of getting rid of it

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2
Q

Explain the dichotomy of iron:

A

iron deficiency is the most common nutritional disorder in the world but hereditary hemochromatosis (iron overload) is one of the most common genetic disorders

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3
Q

What is the relationship between iron and pathogens?

A

Iron is essential for both humans and pathogens; while the body limits free iron to prevent microbial growth (nutritional immunity), pathogens counteract this by scavenging iron through specialized mechanisms, and excess iron can increase infection risk

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4
Q

what environmental factors favour what kind of iron traits?

A

high risk of infection: reduced iron retention to decrease energy for pathogens

survival during famine: increased Fe absorption and retention for O2 transport and cellular metabolism

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5
Q

what are commmon needs for Fe in the body?

A

1) O2 transport
-binding to Hb
2) Structural component of ETC complexes
3) production of cholrophyll
4) catalyst of free radical rxn’s
-ability to change oxidation state

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6
Q

what is hepcidin? where does it come from and what does it do?

A

an antimicrobial peptide in urine that has weak microbicidal activity
-comes from the liver and kills bacteria

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7
Q

what is the relation between hepcidin and iron?

A

the supression of hepcidin causes iron overload
-hepcidin is vital for iron homeostasis

hepcidin will lower [iron] –> decreasing microbial growth

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8
Q

what type of mineral is iron considered to be? how much is needed a day for men and women ages 19-50?

A

micromineral
8mg/day for men
18mg/day for women

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9
Q

what 2 transition states is iron foiund in?

A

ferrous: 2+
ferric: 3+

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10
Q

what is the difference between heme and non-heme iron? provide examples of each.

A

heme iron: major Fe-containing protein that carries O2 thoughout the body
-more readily absorbed
-found in animal sources
-hemo/myoglobin, cyt P450, catalases, peroxidases

non-heme iron: important for O2 transport and metabolism
-not as readily absorbed
-tightly regulated by bodily needs
-Found in plant sources
-Fe-S clusters, oxygen bridged Fe, single Fe atoms

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11
Q

explain the structure of hemoglobin:

A

4 heme subunits to form hemoglobin
-transports up to 4 O2 molecules

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12
Q

what type of iron is present in the ETC? provide examples

A

heme and non-heme iron is present
heme: cytochromes
non-heme: Fe-S clusters

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13
Q

what is the function of cytochrome P450? what is integral to its structure to do this?

A

involved in detoxification of drugs
-Fe atom in heme group involved to take up electrons

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14
Q

what is an example of a protein with oxegym-bridged iron? what is its function?

A

ribonucleotide reductase
-converts ribonucleotides into deoxyribonucleotides
-needed for DNA transcription

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15
Q

what is an example of a single-Fe containing metalloenzyme? what is its function?

A

alpha-KG
-post-translational modification of pro-collagen

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16
Q

How is majority of the Fe in our body found? what are the other forms?

A

1) Functional iron (78%)
-hemoglobin (highest- 2/3 of total iron in body)
-myoglobin
heme / non-heme enzymes
2) storage iron (22%)
-ferritin
3) transport iron (0.0001%)
-transferrin

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17
Q

when are iron needs greatest? what is basal iron loss per day? where are these losses coming from?

A

in periods of growth or blood loss

loss for men: 1 mg
loss for women: 0.75mg (doubles during menstratuation)
-also increases during pregnancy, lactation and parturition

-loss from GIT, skin, epithelial lining

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18
Q

how does Fe dependency alter aborption? what is normal absorption for men and women?

A

increased needs will increase absorption
-1mg for men
->1.5mg for women (4-5mg during late stage pregnancy)

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19
Q

what is the AI for infants based on? what is a concern w infamts not being breast fed?

A

the average intake of healthy infants

-lactoferrin in breastmilk is highly bioavailable as compared to Fe found in formula (more Fe fortification needed in formula)

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20
Q

what is the RDA of iron for women taking oral contraceptives? why?

A

10.9 mg
-it is lowered due to altered menstruation

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21
Q

what is the DRI of iron for vegetarians in comparision to non vegetarians?

A

the DRI for vegetarians is 1.8x higher
-normal DRI is 8mg/day for men and 18mg/day for women

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22
Q

how does the RDA of iron for men and women change throughout life? what is it as an infant? ages 19-50? after 50? and during pregnancy? what is the upper limit?

A

M / W, resepectively
infant: 11 / 11
19-50: 8 / 18
50+: 8 / 8
pregnancy: 27

45mg/day

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23
Q

provide 3 examples of meat that are high in Fe:

A

clams, beef liver, oysters

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24
Q

provide 3 examples of grains that are high in Fe:

A

cereals, oatmeal, whole grain foods

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25
provide 3 examples of legumes that are high in Fe:
soybeans, lentils, kidney beans
26
provide 3 examples of fruit / veg that are higher in Fe:
spinach, pumpkin, tomatoes
27
what are sources of heme vs non heme foods? how does absoprtion and intake differ?
heme: only found in animal flesh (40-60%) -10% of daily intake with 25% absorption non heme: all iron in plants -90% of daily intake with 17% absorbed
28
explain the absorption of heme iron. how is this regulated?
1) hydrolysis from Hb in stomach and SI by HCL and proteases 2) heme absorbed intact by heme carrier protein (HCP1) 3) heme hydrolyzed into Fe2+ and protoporphyrin -heme iron under little regulation and stays relatively consistent (little effect from inhibitors)
29
explain the absorption of non-heme iron. how is this regulated?
1) hydrolized in the stomach to mostly form Fe3+ which is released into the SI -may form Fe(OH)3 which is mostly insoluble 2) some Fe2+ which is absorbed by divalent metal transporter 1 (DMT1)
30
what is chelation?
Chelation is the process by which a molecule (called a chelator) binds tightly to a metal ion, forming a stable complex
31
what does an acidic environment and chelation of Fe do to absorption of Fe3+?
it increases Fe3+ absorption
32
what is the primary determinant of Fe balance?
iron absorption -increased needs will increase absorption
33
what specifically causes increased absorption of Fe?
1) increased expression of divalent metal transporter 1 (DMT1) in the intestine, facilitating greater non-heme iron absorption 2) Hepcidin levels decrease, promoting the activity of ferroportin, the iron exporter, which increases iron entry into the bloodstream 3) DCYTB increases when the body has higher iron demands in order to increase absorption of dietary iron
34
what is the role of DCYTB?
DCYTB (Duodenal Cytochrome B) plays a crucial role in the absorption of non-heme iron by facilitating its reduction, a necessary step for intestinal uptake
35
what is the role of ferroportin?
Ferroportin is the only protein that exports iron from cells into the bloodstream -Ferroportin transports Fe²⁺ across the cell membrane to the extracellular space.
36
what impact does hepcidin have on ferroportin?
When iron levels are high, hepcidin binds to ferroportin, causing its internalization and degradation, halting iron export into the bloodstream
37
explain the phases of iron absorption:
1) ~15mg from diet 2) ~7.5mg available from ferrous (Fe2+) form 3) actual amount taken up by mucosal cells into ferritin is ~4mg 4) final amount released into plasma ~1.5 - 2mg
38
what 3 factors increase Fe absorption?
1) meat factor protein 2) vit C -its acidity solubilizes Fe3+ into Fe2+ 3) acids / sugar (ascorbic, citric, lactic) -facilitate non heme absorption
39
what 3 factors decrease Fe absorption?
1) phytates, polyphenols, fibres, soy, whole grains, and nuts 2) some acids (oxalates, tannic acid) -spinach,beets,rhubarb, tea,coffee 3) some minerals (Ca, Zn, Mn, Ni 4) EDTA
40
Which form of iron has higher absorption efficiency, Fe²⁺ or Fe³⁺?
Fe²⁺ (ferrous iron) has higher absorption efficiency than Fe³⁺ (ferric iron)
41
Why are ferrous salts (Fe²⁺) used in iron supplements? provide 3 examples of the ferrous salts.
Because Fe²⁺ is more bioavailable and has higher absorption rates compared to ferric salts (Fe³⁺) -lactate, fumarate, citrate
42
What is the main reason ferric iron (Fe³⁺) salts have lower absorption rates?
They require additional reduction to Fe²⁺ before absorption, making the process less efficients
43
What is the primary transporter of ferrous iron (Fe²⁺) into enterocytes?
Divalent Metal Transporter 1 (DMT1)
44
What are the two key forms of iron chelation, and why are they important?
Loose chelation: Enhances solubility (e.g., citrate, ascorbate) Tight chelation by phytates/polyphenols: Reduce iron bioavailability by binding it tightly, making it less absorbable -increased fecal excretion
45
what are chelators?
molecules or proteins that bind metal ions
46
What is the primary difference between heme and non-heme iron absorption mechanisms?
Heme iron is absorbed intact via specific transporters. Non-heme iron requires reduction (Fe³⁺ → Fe²⁺) before transport by DMT1.
47
What is the role of hephaestin in iron metabolism?
Hephaestin oxidizes Fe²⁺ to Fe³⁺ after it is exported by ferroportin, enabling it to bind to transferrin in the bloodstream
48
what are 4 recommendations to maximize iron intake?
1) Fe enriched foods (grains) 2) Co-nutrients to increase bioavailibility -Meat factor protein (ham + beans) Vit C 3) Fe cookware 4) supplements
49
what are 2 major factors tat influence iron availibility?
1) turnover (recycling) 2) excretion -GI, skin, urine, large blood losses
50
what is transferrin receptor 1?
a principal protein for transferrin iron uptake (Fe3+) -subject to regulation by regulatory proteins
51
what is Transferrin receptor 2?
secondary protein for transferrin iron uptake -not subject to regulation by regulatory proteins
52
what is ceruloplasmin?
an oxidase that oxidizes Fe2+ to Fe3+ before it is incorporated into apotransferrin
53
what is STEAP?
metalloreductase in endosomes that reduces Fe3+ to Fe2+ before being transported by DMT1
54
when do we need the MOST iron? how much is needed
during erithropoiesis -requires ~24mg Fe daily (17mg in Hb incorporated into Hb)
55
What is the highest priority of Fe usage? why can this be an issue?
formation of heme/globins takes prescedence over other uses of iron when it is limited -other functions may be sacrificed, causing adverse impacts like anemia
56
what makes Hb levels a long term indicator of Fe levels?
iron must be deficient for a long time before seeing depletion of Hb, due ot the priority of Hb formation when Fe is low -2 to 6 weeks to increase Hb with increased Fe intake
57
What is the role of transferrin in iron transport? how much iron can it carry? what type?
transferrin has a higher affinity for ferric iron (Fe³⁺) and binds to it for transport in the plasma. Each transferrin molecule can carry two Fe³⁺ ions but usually only 30% saturated
58
what is serum tranferrin comprised of?
1) apotransferrin - has no Fe bound (high binding affinity) 2) monoferric transferrin- protein bound to iron 3) diferric transferrin- protein bound to 2 irons (fully saturated)
59
how is transferrin saturation calculated? what is the relationship with [transferrin]?
TSAT = [serum iron] / total iron binding capacity (TIBC) x 100 it is inversely proprtional to [transferrin]
60
what is the normal [transferrin] in the plasma? what is the total binding potential?
1) 30mmol / L 2) 60mmol/L
61
what does transferrin stauration < 30% , <15% and >60% indicate?
<30% : depleted iron stores <15% : iron deficient erythropoesis >60%: dangerous excess
62
what would you expect to see for transferrin levels in early iron deficiency, through to more severe deficiency?
1) serum TF increases initially to attempt to increase Fe transport -normal serum iron levels (low-normal saturation % + high TIBC) 2) after iron stores are depleted, serum TF are still elevated but serum Fe will be low (low saturation % + very high TIBC)
63
what is the role of ferritin?where are major location sites? what is the nromal range of ferritin levels?
storage of Fe in a safe, non-toxic, bioavailable form -spleen, liver,skeltal muscle, serum (reflects iron stores) -18-270 for men and 18-160 for women
64
what is apoferritin? what subunits does it contain? what can you expect of the function and proportion of these units?
ferritin without iron 1) L subunit (storage type) - ~30% 2) H subuint (site of Fe2+ oxidation to form Fe3+)
65
What triggers the production of Hepcidin, and what is its function?
Hepcidin is produced by high iron levels and inflammation. 1) It inhibits ferroportin, reducing iron absorption from the gut (decreasing Fe supply) 2) limits Fe to pathogens to prevent toxicity
66
What are the steps of the transferrin cycle in iron transport?
Iron Binding: Transferrin binds Fe³⁺ (ferric iron) in the bloodstream, forming holotransferrin. Receptor Interaction: Holotransferrin binds to transferrin receptors (TfR1) on cell membranes. Endocytosis: The transferrin-receptor complex is internalized into endosomes. Iron Release: At the acidic pH of endosomes, Fe³⁺ is released, reduced to Fe²⁺ by STEAP3, and transported into the cytoplasm by DMT1. Recycling: Apotransferrin (iron-free transferrin) and TfR1 are recycled back to the cell surface, and apotransferrin dissociates into the bloodstream.
67
What is the significance of soluble transferrin receptor (sTfR) levels in blood?
sTfR circulates as transferrin + receptor complex and indicates iron levels High sTfR levels indicate iron deficiency as the body increases receptor expression to compensate for low iron. Low sTfR levels indicate decreased erythropoiesis (less Fe needed)
68
what do you expect of sTfR levels for anemia is due to factors such as inflammation and not iron deficiency?
the sTfR levels would be normal
69
What are iron-responsive elements (IREs), and how do they function? what do you expect during low and high Fe conditions?
IREs regulate protein production based on iron levels: Low iron: IRE-binding proteins attach to IREs, preventing ferritin production (to avoid storing iron) and stabilizing transferrin receptor mRNA (to increase iron uptake). High iron: IRE-binding proteins are inactive, allowing ferritin to store iron and reducing transferrin receptor expression to limit iron uptake.
70
What are the stages of iron deficiency?
Iron storage depletion: Low serum ferritin, no functional impact (Heme-containig proteins have increase Fe priority) Mild deficiency without anemia: decreased Fe transport due to iron-deficient RBC formation -decreased RBC size Iron-deficiency anemia: Measurable deficits in hemoglobin
71
What are the functional consequences of iron deficiency?
Impaired work capacity and cognitive function Delayed psychomotor and immune function in children Pregnancy complications, including low birth weight and increased perinatal mortality
72
when Fe stores are depleted, what do you expect of TIBC levels? what about serum ferritin levels?
increased levels ( >400 micro g/L) decreased levels (< 12 micro g/L)
73
during early Fe deficiency, what do you expect of transferrin saturation? what about serum transferrin receptor?
1) decreased levels (< 16%) 2) increased levels (> 8.5micro g/L)
74
what do you expect of [Hb] in an anemic person?
decreased to < 130 g/L
75
what do you expect the hepcidin, ferritin, and sTfr levels to be for Fe deficient individuals vs individuals w inflamation?
76
Who is at the highest risk for iron deficiency?
Infants, especially preterm or low birth weight, due to limited stores and low iron in breast milk. Children and teens during growth spurts. Women of childbearing age due to menstruation and pregnancy
77
why do kids multivitamins not conatin Fe?
there is a large risk for toxicity if kids overcomsume the vitamin
78
what are main causes of Fe deficiency?
1) increased growth demands 2) limited intake, malabsorption, drug interference 3) increased losses (blood loss, donation)
79
What dietary recommendations maximize iron intake?
Pair non-heme iron sources (e.g., vegetables) with Vitamin C to enhance absorption. Include heme iron sources like meat. Avoid inhibitors like calcium and tannins during iron-rich meals
80
What is hereditary hemochromatosis, and how does it cause iron toxicity? what are symptoms? who is at higher risk and why?
mutations in the HFE gene impair Hepcidin regulation, leading to excessive iron absorption (2-3x normal amount) and storage. Symptoms include fatigue, joint pain, and organ damage older men at higher risk due to lack of Fe loss, resulting in cumulative effects over the lifespan